Abstract

The aim of this study is to investigate the resistance of DNA methyltransferase (MGMT) in gliomas or brain metastases of melanoma to Temozolomide (TMZ) therapy. The in-vivo effects of standard, metronomic and dose-dense TMZ regimens in animal models were monitored to identify efficacy of those regimens with respect to suppression of MGMT-resistance in tumor cells. MGMT-resis
tance is dependent mainly on the TMZ dose/day of the applied regimen, observed when applying standard regimens of 2.45 mg/kg bw/day for 5 days every 28 days and maximized by increasing dose/day to 6.74 mg/kg bw/day for 5 days every 28 days. Afterwards, MGMT-resistance decreased gradually until being suppressed by increasing the received dose/day in standard regimen to 8.88 mg/kg bw/day for 5 days every 28 days. Standard regimen of dose less than 4.37 mg/kg bw/day for 5 days every 28 days is more efficient than the metronomic one of dose/day less than 0.78 mg/kg bw/day for 28 days in early stages of primary tumors.

While the metronomic regimen of dose/day lies between 0.78 and 1.6 mg/kg bw/day for 28 days is more efficient than the standard one of administered dose lies between 4.37 and 8.96 mg/kg bw/day for 5 days every 28 days in the moderate stages of recurrent tumors of higher MGMT-resistance. Dose-dense regimens with standard schedule of dose/day higher than 8.96 mg/kg/bw/day for 5 days every 28 days or metronomic schedule of dose/day higher than 1.6 mg/kg bw/day for 28 days suppress MGMT-mediated resistance in advanced stages of high-grade tumors by depleting MGMT in tumor cells.

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Special Issue on ReviewsActa Scientific Journals has been started Special Issue on Reviews, researchers from world wide welcoming for submission of their reviews on any topic by on/ before September 15, 2019. Special Issue is going to be released on October 01, 2019